STI Treatment Guidelines: Screening, Diagnosis & Treatment

Patricia Pichilingue-Reto MD, FAAP, AAHIVSAssistant Professor of PediatricsPediatric Infectious Diseases (LSU Health Shreveport)

Sexually transmitted infections continue to rise across the United States, andLouisiana consistently ranks among the highest-burden states. Primary careclinicians, pediatricians, and adolescent-health providers are on the front lineof screening, diagnosis, and treatment. This reference distills the current CDCapproach to the STIs seen most often in adolescents and adults — chlamydia,gonorrhea, syphilis, trichomoniasis, Mycoplasma genitalium, pelvic inflammatorydisease, and HIV — into a practical, at-a-glance format. It covers how to take afocused sexual history, who to screen and at which anatomic sites, currentfirst-line and alternative regimens, and the serologic and HIV testing algorithms.It also flags what has changed since 2021: doxycycline post-exposure prophylaxis(doxyPEP) and the ongoing benzathine penicillin shortage. Drug regimens andavailability change; always confirm current CDC guidance before prescribing.

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Sexually transmitted infections continue to rise in the United States, and Louisiana consistently ranks among the highest-burden states. This reference summarizes the current CDC approach to screening, diagnosis, and treatment of common STIs in adolescents and adults, based on the CDC STI Treatment Guidelines, 2021 and the notable updates issued since — including doxycycline post-exposure prophylaxis (doxyPEP) and the ongoing benzathine penicillin (Bicillin L-A) shortage.
Clinical use note: Regimens and dosing below are provided for reference and reflect CDC guidance current at the time of adaptation. STI guidance changes; drug availability changes. Confirm the current CDC STI Treatment Guidelines and any active CDC advisories before prescribing, and account for allergies, pregnancy, site of infection, and local resistance.

Taking a sexual history: the Five P's

An accurate, nonjudgmental sexual history drives appropriate screening. The CDC frames it around five domains — ask openly and adapt to the patient:

  • Partners — whether currently sexually active, and the number and gender(s) of partners
  • Practices — the types of sexual contact (vaginal, anal, oral), which drive site-specific testing
  • Protection from STIs — condom and prevention practices, and interest in PrEP/doxyPEP
  • Past history of STIs — prior testing, prior diagnoses, partner history; injection-drug use for HIV/hepatitis risk
  • Pregnancy intention — desire for pregnancy and current contraception

Screening at a glance

Screening recommendations differ by population and by anatomic site of exposure. Test at the sites where exposure occurs — the 2021 guidelines emphasize extragenital (rectal and pharyngeal) testing where indicated.

Women & heterosexual men

  • Chlamydia & gonorrhea: women <25, and older women at increased risk, screened annually
  • Self-collected vaginal swab is acceptable
  • Heterosexual men: consider chlamydia screening in high-prevalence settings (adolescents, corrections, STI clinics)
  • Retest ~3 months after treatment (reinfection)

Men who have sex with men (MSM)

  • HIV (4th-generation Ag/Ab), syphilis serology
  • Chlamydia & gonorrhea by NAAT at exposed sites (urethral, rectal, pharyngeal)
  • Hepatitis A, B; hepatitis C if HIV-positive
  • At least annually; every 3–6 months if higher risk
HIV, everyone: Test all adolescents and adults aged 13–64 at least once; anyone seeking STI evaluation should be tested for HIV at each visit for a new complaint, regardless of known risk.

Chlamydia

Preferred: doxycycline 100 mg orally twice daily for 7 days. Randomized and meta-analytic data show doxycycline outperforms single-dose azithromycin, with the difference most pronounced for rectal infection (where doxycycline is clearly superior) and symptomatic urethritis in men. Rectal chlamydia is common even among women with genitourinary infection. Azithromycin 1 g orally once remains an alternative (e.g., adherence concerns, pregnancy) but has lower efficacy at urethral and rectal sites. Retest at ~3 months.

Gonorrhea

Rising azithromycin resistance drove a shift to ceftriaxone monotherapy. Pharyngeal infection is common, under-screened, and harder to cure — obtain a test-of-cure ~7–14 days after treating pharyngeal gonorrhea.

SettingRegimen
PreferredCeftriaxone 500 mg IM once (1 g if ≥150 kg)
If chlamydia not excludedAdd doxycycline 100 mg orally twice daily for 7 days
Cephalosporin allergyGentamicin 240 mg IM + azithromycin 2 g orally once

No reliable alternative exists for pharyngeal gonorrhea in cephalosporin-allergic patients — consult an ID specialist.

What changed from 2015 to 2021

Infection2021 (current)2015 (prior)
GonorrheaCeftriaxone 500 mg IM onceCeftriaxone 250 mg IM + azithromycin 1 g orally once
ChlamydiaDoxycycline 100 mg orally twice daily × 7 daysAzithromycin 1 g orally once

Syphilis: staging and treatment

Benzathine penicillin G remains the treatment of choice across all stages. Note that neurosyphilis, ocular, and otic syphilis require IV aqueous penicillin.

StageRecommendedPenicillin-allergic alternative*
Primary, secondary, early latentBenzathine penicillin G 2.4 million units IM onceDoxycycline 100 mg orally twice daily × 14 days
Late latent / unknown durationBenzathine penicillin G 2.4 million units IM weekly × 3Doxycycline 100 mg orally twice daily × 28 days
Neuro / ocular / oticAqueous crystalline penicillin G IV × 10–14 daysConsult ID; consider desensitization

*Doxycycline is not an option in pregnancy. For syphilis in pregnancy, penicillin is the only recommended treatment; penicillin-allergic pregnant patients require desensitization.

The 2021 guidelines also note that a lumbar puncture is not required for isolated ocular or otic syphilis in the absence of cranial-nerve deficits.

Bicillin L-A shortage (active): Benzathine penicillin G (Bicillin L-A) has been in national shortage, compounded by a 2025 lot recall. CDC recommends prioritizing available supply for pregnant patients and infants with congenital syphilis, for whom penicillin is the only recommended treatment. FDA has permitted temporary importation of alternative benzathine formulations (Lentocilin, Extencilline). Check current CDC and Louisiana Department of Health advisories for supply status before treating.

Syphilis serologic testing

Diagnosis uses a two-test strategy combining a treponemal and a nontreponemal test. Two sequencing approaches are in use:

Nontreponemal test (RPR or VDRL) Reactive Nonreactive Treponemal test (FTA-ABS, TPPA, EIA) No serologic evidence Reactive Nonreactive Evidence of syphilis (current or prior) Likely false positive
Traditional algorithm: nontreponemal screen first, treponemal test to confirm. Concept adapted from the standard CDC two-test serologic strategy; redrawn by LA AAP.
Screening treponemal immunoassay (EIA/CIA) Reactive Nonreactive Nontreponemal test (RPR or VDRL) No serologic evidence Reactive Nonreactive Evidence of syphilis TPPA Reactive Nonreactive False positive vs. early infection
Reverse-sequence algorithm: treponemal immunoassay screen first, then nontreponemal test, with TPPA to resolve discordant results. Concept adapted from the standard CDC reverse-sequence strategy; redrawn by LA AAP.

Trichomoniasis

  • Women: metronidazole 500 mg orally twice daily for 7 days (a multi-day course, changed from single-dose)
  • Men: metronidazole 2 g orally once
  • Alternative: tinidazole 2 g orally once
  • Retest women <3 months after treatment (high reinfection), regardless of partner treatment status

Mycoplasma genitalium

M. genitalium is an increasingly recognized cause of nongonococcal urethritis, cervicitis, and PID, with macrolide resistance widespread. Treatment is sequential and depends on resistance testing:

  • Macrolide sensitive: doxycycline 100 mg twice daily × 7 days, then azithromycin (1 g, then 500 mg daily × 3 days)
  • Macrolide resistant, or resistance testing unavailable: doxycycline 100 mg twice daily × 7 days, then moxifloxacin 400 mg daily × 7 days

Pelvic inflammatory disease (PID)

Diagnose empirically in a sexually active young woman with pelvic/lower-abdominal pain and at least one of: cervical motion tenderness, uterine tenderness, or adnexal tenderness. A key 2021 change: metronidazole is now added routinely for anaerobic coverage.

SettingRepresentative regimen
Outpatient (IM/oral)Ceftriaxone 500 mg IM once + doxycycline 100 mg orally twice daily × 14 days + metronidazole 500 mg orally twice daily × 14 days
ParenteralCeftriaxone 1 g IV q24h + doxycycline + metronidazole (or a cefotetan/cefoxitin-based regimen)

Consider hospitalization for: inability to exclude a surgical emergency, tubo-ovarian abscess, pregnancy, severe illness or intractable vomiting, inability to tolerate oral therapy, or no response to oral treatment.

HIV testing algorithm

Current laboratory diagnosis starts with a 4th-generation antigen/antibody combination immunoassay, with reflex differentiation and, when needed, a nucleic acid test to catch acute infection:

HIV-1/2 Ag/Ab combination immunoassay Reactive Nonreactive HIV-1/HIV-2 antibody differentiation immunoassay Negative for HIV-1 & HIV-2 HIV-1 or HIV-2 Ab + Neg / indeterminate HIV antibodies detected HIV-1 NAT Positive Negative Acute HIV-1 infection Negative for HIV-1
Laboratory HIV testing algorithm. Concept adapted from the standard CDC/APHL recommended testing algorithm; redrawn by LA AAP.

Prevention: what's changed since this talk

The source presentation predates two developments every Louisiana clinician caring for sexually active adolescents and adults should know:

doxyPEP (CDC, 2024): Doxycycline 200 mg taken within 72 hours after sex reduces bacterial STIs in higher-risk populations. CDC recommends that MSM and transgender women who have had a bacterial STI (syphilis, chlamydia, or gonorrhea) in the past 12 months receive counseling and, through shared decision-making, be offered a doxyPEP prescription. It should sit within comprehensive sexual-health care, with STI testing at exposed sites every 3–6 months and linkage to HIV PrEP where appropriate.

Alongside doxyPEP: continue to inform all sexually active adolescents and adults about HIV PrEP, use expedited partner therapy (EPT) where legal and appropriate for chlamydia and gonorrhea, and offer HPV and hepatitis A/B vaccination.

Adapted by the Louisiana Chapter of the American Academy of Pediatrics from a continuing-education presentation, Update on Sexually Transmitted Infections (STI) Guidelines, by Patricia Pichilingue-Reto, MD, FAAP, AAHIVS (LSU Health Shreveport, Pediatric Infectious Diseases). Clinical content on this page is restated in original form from the CDC Sexually Transmitted Infections Treatment Guidelines, 2021 (Workowski KA, Bachmann LH, Chan PA, et al. MMWR Recomm Rep. 2021;70(4):1–187), a US-government work, and updated to reflect the CDC doxyPEP guidelines (2024) and current benzathine penicillin supply advisories. The syphilis and HIV decision diagrams were redrawn by LA AAP from the standard CDC testing strategies.

This page is educational and does not indicate an exclusive course of treatment or serve as a standard of medical care; variations accounting for individual circumstances may be appropriate. Regimens, dosing, and drug availability change — clinicians must verify against the current CDC STI Treatment Guidelines, active CDC advisories, and Louisiana Department of Health guidance before prescribing.